Strategien und Elektrodendesign für die patientenindividuelle tumortherapeutische Anwendung der Elektroporation

  • Strategies and electrode design for the patient-customized application of electroporation in tumor therapy

Ritter, Andreas; Schnettler, Armin (Thesis advisor); Baumann, Martin (Thesis advisor)

Aachen (2017)
Dissertation / PhD Thesis

Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2017

Abstract

With about 220000 cancer-related deaths per year, malignant tumors are the second most common cause of death in Germany. In case of operability, surgical resection of the primary tumor and its metastases is the treatment of choice, but this option is only available for a minority of patients because of tumor spread and/or comorbidities.As an alternative to chemotherapy, various minimally invasive endovascular and percutaneous tumor treatments have gained clinical acceptance. Widespread treatments are percutanoeus thermal ablation procedures like radiofrequency ablation (RFA) or microwave ablation (MWA), both using different technologies to apply heat to destroy the tumor.Irreversible electroporation (IRE) and electrochemotherapy (ECT) are two new, innovative electroporation-based minimally-invasive therapies for the treatment of cancer. Combining non-thermal properties of IRE with local application of chemotherapy, ECT is an established treatment modality for superficial malignancies of the skin. Since the application of ECT in solid organs is a promising approach, this dissertation describes the development of a prototype applicator for ECT in solid organs.For a better understanding of the effects described above, an in vitro model for the medical application of IRE has been developed. Multiple studies made with this model provide information about the required amount of electric field strength to ensure absolute cell death in correlation to different cell lines.Using CAD design and FEM computer simulations, a complete new needle-shaped multipolar probe with telescopic electrodes for percutaneous image-guided IRE as well as ECT in solid organs has been developed. A fully functional prototype of the applicator contains four expandable hollow electrodes in a semicircular configuration used for both: interstitial injection of the chemotherapeutic agent and generation of the electric field.With the prototype it is possible to place five independent electrodes doing a single stitch only, which has major advantages for IRE (time of the intervention, accuracy, risk of needle tract seeding). Results of the first in vivo trials show an excellent accordance of simulated and measured ablation volumes. The promising results for ECT legitimate the redesign of an multipole electroporation system to vary tumor coverage per software, even after the electrodes were positioned. The prototype already covers this concept and a hard- and software design for this purpose is also included in this dissertation.To rate the direct effects, a Q factor model with weighting coefficients has been developed to optimize the geometric and electric parameters dispassionately. In clinical applications, this will enable the physician to adapt the desired ablation zone to the patient individual 3D tumor geometry. It is also possible, that an electroporator will correct small deviations in the intended location of each electrode, by adapting the potential of all electrodes individually.To conclude, an integrated workflow for a case-specific clinical application has been designed: Patient-customized electroporation therapy (PACET).